Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by ra...Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining homeostasis.Hence,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful response.Anti-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for survival.At the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral tissues.Additionally,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).展开更多
Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting dist...Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.展开更多
With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the pr...With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.展开更多
Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in Dec...Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).展开更多
Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evi...Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.展开更多
Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemi...Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemia,haemorrhage and neuroinflammation,which over time result in further neural tissue loss.Eventually,at chronic stages of traumatic spinal cord injury,the formation of a glial scar,cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal regrowth.This is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous system.The intracellular signalling molecule,cyclic adenosine 3′,5′-monophosphate(cAMP),is known to play many important roles in the central nervous system,and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal models.However,therapies directly targeting cAMP have not found their way into the clinic,as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects.A downstream effector of cAMP,exchange protein directly activated by cAMP 2(Epac2),is mainly expressed in the adult central nervous system,and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and regeneration.Recently,using ex vivo modelling of traumatic spinal cord injury,Epac2 activation was found to profoundly modulate the post-lesion environment,such as decreasing the activation of astrocytes and microglia.Pilot data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord injury.Therefore,targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair,and future work is needed to fully establish its therapeutic potential.展开更多
Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements.We postulate th...Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements.We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation.CSC can be the key to the elaboration of anti-cancer-based therapy.In this article,we focus on a controversial new theme relating to CSC.Tumorigenesis may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological events.Identifying such a stage can allow the production of more effective therapies (e.g.manipulated stem cells) to treat several cancers.More importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC.This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells.Currently,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC.Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer.The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g.normal stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.展开更多
1997年在英国北部一个叫纽卡斯尔（Newcastle upon Tyne）（图1）的城市里发生了一件与卒中学术研究＂无关＂的小事,但这件小事在10年后却改变了整个卒中世界。1996年美国食品药品监督管理局（Food and Drug Administration,FDA）批准...1997年在英国北部一个叫纽卡斯尔（Newcastle upon Tyne）（图1）的城市里发生了一件与卒中学术研究＂无关＂的小事,但这件小事在10年后却改变了整个卒中世界。1996年美国食品药品监督管理局（Food and Drug Administration,FDA）批准了对急性缺血性卒中患者在发病3 h内使用阿替普酶溶栓,从此开始了溶栓治疗卒中的时代。展开更多
Nanotechnology offers exciting new approaches for biology and medicine. In recent years, nanoparticles,particularly those of the rare metal cerium, are showing potential for a wide range of applications in medicine.Ce...Nanotechnology offers exciting new approaches for biology and medicine. In recent years, nanoparticles,particularly those of the rare metal cerium, are showing potential for a wide range of applications in medicine.Cerium oxide nanoparticles or nanoceria are antioxidants and possess catalytic activities that mimic those of super oxide dismutase and catalase, thereby protecting cellsfrom oxidative stress. The retina is highly susceptible to oxidative stress because of its high oxygen consumption and high metabolic activity associated with exposure to light. Many retinal diseases progress through oxidative stress as a result of a chronic or acute rise in reactive oxygen species. Diseases of the retina are the leading causes of blindness throughout the world. Although some treatments may delay or slow the development of retinal diseases, there are no cures for most forms of blinding diseases. In this review is summarized evidence that cerium oxide nanoparticles can function as catalytic antioxidants in vivo in rodent models of age-related macular degeneration and inherited retinal degeneration and may represent a novel therapeutic strategy for the treatment of human eye diseases. This may shift current research and clinical practice towards the use of nanoceria, alone or in combination with other therapeutics.展开更多
Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing s...Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing sizable and desirable cellular elements, it has been attended in the field of regenerative medicine, which will hopefully provide novel therapeutic strategies for currently incurable diseases, such as varieties of central nervous system (CNS) diseases and injuries. In this article, we will first discuss naturally occurring and experimentally induced dedifferentiation, and then set forth principles in stem-cell based therapy in the neural field;beyond that, we will introduce two recent studies that show dedifferentiated stem cells contribute to neural regeneration. Moreover, we also present our recent research results of dedifferentiated muscle stem cells for neurogenic differentiation study in vitro. Further work will be conducted to elucidate the mechanism underlying the dedifferentiation process to facilitate the development of new strategies in regenerative medicine.展开更多
Background:Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-sa...Background:Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-saccade task.Decline in cognitive control has been attributed to normal aging and neurological illnesses such as Parkinson’s disease(PD)as well as decline in other cognitive abilities.This parallel might highlight the role played by cognitive control in information processing and working memory.However,little is known about the relationship between cognitive control and other cognitive processes such as visual memory,decision making,and visual search.We thus propose to correlate the incidence of impaired cognitive control with deficits in visual memory,decision making and visual search in three groups:younger adults,older adults and patients with idiopathic PD.Methods:Seventy-one participants,namely 34 adults(M=22.75,SD=3.8),22 older adults(M=67.4,SD=8.3),and 20 PD patients(M=65.59,SD=8.2)performed four tasks:interleaved pro/anti-saccade,visual memory,decision making,and serial and pop-out visual search.Results:Results show that within each group,anti-saccade error rate(ER)were significantly and negatively correlated with visual memory ER(ryounger=−0.378,P=0.036;rolder=−0.440,Polder=0.046;rPD=−0.609,P=0.016).On the other hand,correct decision-making reaction times(RT)were significantly correlated with anti-saccade ER,and RTs only in older adults(rER=0.529,P=0.014;rRT=0.512,P=0.018)and PD patients(rER=0.727,P=0.012;rRT=0.769,P=0.001).For visual search,PD patients showed a significant relationship between RTs for correct pro-saccades and pop-out(r=0.665,P=0.007),and serial(r=0.641,P=0.010)search RTs.Furthermore,there was a significant correlation between MoCA scores and anti-saccade RTs(r=−0.559,P=0.030)and ER(r=−0.562,P=0.029)in PD patients.Taken together,these results support the hypothesis of PD patients’reliance on bottom-up processes as top-down processes decline.For younger adults,there was a significant correlation between serial search performance and both anti-saccade ER(r=0.488,P=0.005),and correct pro-saccade ER(r=0.413,P=0.021).In older adults,this relationship was absent,but anti-saccade ER significantly correlated with pop-out search times(r=0.473,P=0.030).Conclusions:We found significant relationships between cognitive tasks and cognitive control as measured through the interleaved pro/anti-saccade task across and within participant groups,providing evidence of the appropriateness of the use of the interleaved pro/anti-saccade task as a measure of overall cognitive control.展开更多
Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associa...Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associated gene.The abnormal expansion translates into a protein bearing an abnormally long tract of glutamines.展开更多
The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specializ...The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specialized molecular machinery is strategically placed to release and receive neurotransmitters and to generate and extinguish calcium(Ca^(2+))signals.These synaptic molecular components are highly dynamic and they influence each other to confer structural and functional adaptability(plasticity)to neuronal communication(Biederer et al.,2017).展开更多
Objective To investigate the role of extracellular signal-regulated kinase1/2(ERK1/2) pathway in the regulation of aquaporin 4(AQP4) expression in cultured astrocytes after scratch-injury. Methods The scratch-injury m...Objective To investigate the role of extracellular signal-regulated kinase1/2(ERK1/2) pathway in the regulation of aquaporin 4(AQP4) expression in cultured astrocytes after scratch-injury. Methods The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase(LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2(p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 μmol/L U0126(ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups. Results Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury. Conclusion These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.展开更多
Attention deficit hyperactivity disorder(ADHD) is a pervasive psychiatric disorder that affects both children and adults. Adult male and female patients with ADHD are differentially affected, but few studies have expl...Attention deficit hyperactivity disorder(ADHD) is a pervasive psychiatric disorder that affects both children and adults. Adult male and female patients with ADHD are differentially affected, but few studies have explored the differences. The purpose of this study was to quantify differences between adult male and female patients with ADHD based on neuroimaging and connectivity analysis. Resting-state functional magnetic resonance imaging scans were obtained and preprocessed in 82 patients. Group-wise differences between male and female patients were quantified using degree centrality for different brain regions. The medial-, middle-, and inferior-frontal gyrus, superior parietal lobule, precuneus, supramarginal gyrus, superior- and middle-temporal gyrus, middle occipital gyrus, and cuneus were identified as regions with significant group-wise differences. The identified regions were correlated with clinical scores reflecting depression and anxiety and significant correlations were found. Adult ADHD patients exhibit different levels of depression and anxiety depending on sex, and our study provides insight into how changes in brain circuitry might differentially impact male and female ADHD patients.展开更多
AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using n...AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously.Visceral hypersensitivity was evaluated using electromyographic(EMG)responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions(CRD).Abdominal withdrawal reflex(AWR)scores and pain thresholds were also detected in adult rats.Different doses of ZD7288(25,50,and 100 nmol/L)were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.RESULTS:EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats(P<0.05).The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats(P<0.05).Treatment with50-100 nmol/L ZD 7288 significantly inhibited EMG responses(16%-62%,80-20 mmHg CRD,P<0.05)and AWR scores(24%-37%,40-20 mmHg CRD,P<0.05;12%-61%,80-20 mmHg CRD,P<0.05,respectively),and significantly increased pain thresholds(32%-77%,P<0.05).CONCLUSION:Spinal HCN channels may play an important role in chronic visceral hypersensitivity.展开更多
Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB...Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against NMDA-induced retinal damage.In this study,Sprague-Dawley rats were randomized to undergo intravitreal injection of vehicle,NMDA or MgAT as pre-treatment to NMDA.Seven days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRN3A immunostaining.Functional outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain reaction.Retinal phospho-NF-κB,phospho-p53 and AP-1 levels were evaluated using western blot assay.Rat visual functions were evaluated using visual object recognition tests.Both retrograde labelling and BRN3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of NMDA.Electroretinography indicated that pre-treatment with MgAT partially preserved the functional activity of NMDA-exposed retinas.MgAT abolished NMDA-induced increase of retinal phospho-NF-κB,phospho-p53 and AP-1 expression and suppressed NMDA-induced transcriptional activity of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(i.e.objects with different shapes)after NMDA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with MgAT.In conclusion,pre-treatment with MgAT prevents NMDA induced retinal injury by inhibiting NMDA-induced neuronal apoptosis via downregulation of transcriptional activity of NF-κB,p53 and AP-1-mediated c-Jun/c-Fos.The experiments were approved by the Animal Ethics Committee of Universiti Teknologi MARA(UiTM),Malaysia,UiTM CARE No 118/2015 on December 4,2015 and UiTM CARE No 220/7/2017 on December 8,2017 and Ethics Committee of Belgorod State National Research University,Russia,No 02/20 on January 10,2020.展开更多
基金supported by grants from the Spanish Ministry of Education and Science(RYC-2017-22412,PID2019-107989RB-I00 and MDM-2017-0720)FundacióTV3(248/C/2020)(to AM).
文摘Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining homeostasis.Hence,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful response.Anti-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for survival.At the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral tissues.Additionally,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).
基金supported by NIH grants NS084967,NS121037 (to AEK) and NS110609 (to COB)。
文摘Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.
基金supported by The David and Inez Myers Foundation,Beachwood,OH,USA(to DT)。
文摘With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.
基金sponsored by a grant from the National Institute of Neurological Disorders and Stroke:RO1NS116059(to MZ)。
文摘Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).
基金the following financial support grant FAR-2019 to DL from The Universita del Piemonte Orientale。
文摘Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.
基金supported by Scottish Rugby Union funding to WH and DSthe NRB PhD scholarship from the International Spinal Rsesarch Trust to AGBa Hot-Start Scholarship from the University of aberdeen to DD。
文摘Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemia,haemorrhage and neuroinflammation,which over time result in further neural tissue loss.Eventually,at chronic stages of traumatic spinal cord injury,the formation of a glial scar,cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal regrowth.This is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous system.The intracellular signalling molecule,cyclic adenosine 3′,5′-monophosphate(cAMP),is known to play many important roles in the central nervous system,and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal models.However,therapies directly targeting cAMP have not found their way into the clinic,as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects.A downstream effector of cAMP,exchange protein directly activated by cAMP 2(Epac2),is mainly expressed in the adult central nervous system,and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and regeneration.Recently,using ex vivo modelling of traumatic spinal cord injury,Epac2 activation was found to profoundly modulate the post-lesion environment,such as decreasing the activation of astrocytes and microglia.Pilot data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord injury.Therefore,targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair,and future work is needed to fully establish its therapeutic potential.
基金Supported by CHOC Children’s Foundation and CHOC Neuroscience Institute (to Li SC)Austin Ford Tribute Fund+2 种基金the W.M.Keck Foundation (to Li SC)Grant R21CA134391 from the National Institutes of HealthGrant AW 0852720 from the National Science Foundation (to Zhong JF)
文摘Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements.We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation.CSC can be the key to the elaboration of anti-cancer-based therapy.In this article,we focus on a controversial new theme relating to CSC.Tumorigenesis may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological events.Identifying such a stage can allow the production of more effective therapies (e.g.manipulated stem cells) to treat several cancers.More importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC.This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells.Currently,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC.Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer.The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g.normal stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.
文摘1997年在英国北部一个叫纽卡斯尔（Newcastle upon Tyne）（图1）的城市里发生了一件与卒中学术研究＂无关＂的小事,但这件小事在10年后却改变了整个卒中世界。1996年美国食品药品监督管理局（Food and Drug Administration,FDA）批准了对急性缺血性卒中患者在发病3 h内使用阿替普酶溶栓,从此开始了溶栓治疗卒中的时代。
基金Supported by NIH NEI,No.R21EY018306,R01EY18724,R01EY022111National Science Foundation,No.CBET-0708172
文摘Nanotechnology offers exciting new approaches for biology and medicine. In recent years, nanoparticles,particularly those of the rare metal cerium, are showing potential for a wide range of applications in medicine.Cerium oxide nanoparticles or nanoceria are antioxidants and possess catalytic activities that mimic those of super oxide dismutase and catalase, thereby protecting cellsfrom oxidative stress. The retina is highly susceptible to oxidative stress because of its high oxygen consumption and high metabolic activity associated with exposure to light. Many retinal diseases progress through oxidative stress as a result of a chronic or acute rise in reactive oxygen species. Diseases of the retina are the leading causes of blindness throughout the world. Although some treatments may delay or slow the development of retinal diseases, there are no cures for most forms of blinding diseases. In this review is summarized evidence that cerium oxide nanoparticles can function as catalytic antioxidants in vivo in rodent models of age-related macular degeneration and inherited retinal degeneration and may represent a novel therapeutic strategy for the treatment of human eye diseases. This may shift current research and clinical practice towards the use of nanoceria, alone or in combination with other therapeutics.
文摘Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing sizable and desirable cellular elements, it has been attended in the field of regenerative medicine, which will hopefully provide novel therapeutic strategies for currently incurable diseases, such as varieties of central nervous system (CNS) diseases and injuries. In this article, we will first discuss naturally occurring and experimentally induced dedifferentiation, and then set forth principles in stem-cell based therapy in the neural field;beyond that, we will introduce two recent studies that show dedifferentiated stem cells contribute to neural regeneration. Moreover, we also present our recent research results of dedifferentiated muscle stem cells for neurogenic differentiation study in vitro. Further work will be conducted to elucidate the mechanism underlying the dedifferentiation process to facilitate the development of new strategies in regenerative medicine.
文摘Background:Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-saccade task.Decline in cognitive control has been attributed to normal aging and neurological illnesses such as Parkinson’s disease(PD)as well as decline in other cognitive abilities.This parallel might highlight the role played by cognitive control in information processing and working memory.However,little is known about the relationship between cognitive control and other cognitive processes such as visual memory,decision making,and visual search.We thus propose to correlate the incidence of impaired cognitive control with deficits in visual memory,decision making and visual search in three groups:younger adults,older adults and patients with idiopathic PD.Methods:Seventy-one participants,namely 34 adults(M=22.75,SD=3.8),22 older adults(M=67.4,SD=8.3),and 20 PD patients(M=65.59,SD=8.2)performed four tasks:interleaved pro/anti-saccade,visual memory,decision making,and serial and pop-out visual search.Results:Results show that within each group,anti-saccade error rate(ER)were significantly and negatively correlated with visual memory ER(ryounger=−0.378,P=0.036;rolder=−0.440,Polder=0.046;rPD=−0.609,P=0.016).On the other hand,correct decision-making reaction times(RT)were significantly correlated with anti-saccade ER,and RTs only in older adults(rER=0.529,P=0.014;rRT=0.512,P=0.018)and PD patients(rER=0.727,P=0.012;rRT=0.769,P=0.001).For visual search,PD patients showed a significant relationship between RTs for correct pro-saccades and pop-out(r=0.665,P=0.007),and serial(r=0.641,P=0.010)search RTs.Furthermore,there was a significant correlation between MoCA scores and anti-saccade RTs(r=−0.559,P=0.030)and ER(r=−0.562,P=0.029)in PD patients.Taken together,these results support the hypothesis of PD patients’reliance on bottom-up processes as top-down processes decline.For younger adults,there was a significant correlation between serial search performance and both anti-saccade ER(r=0.488,P=0.005),and correct pro-saccade ER(r=0.413,P=0.021).In older adults,this relationship was absent,but anti-saccade ER significantly correlated with pop-out search times(r=0.473,P=0.030).Conclusions:We found significant relationships between cognitive tasks and cognitive control as measured through the interleaved pro/anti-saccade task across and within participant groups,providing evidence of the appropriateness of the use of the interleaved pro/anti-saccade task as a measure of overall cognitive control.
基金funded by the Portuguese Science and Technology Foundation (FCT) projectby the French Muscular Dystrophy Association(AFM-Téléthon).by the Ataxia UK+1 种基金by the CureCSB project.AndréConceicao and Rebekah Koppenol are supported by Ph.D.fellowships from FCT (DFA/BD/7892/2020SFRH/BD/148533/2019,respectively)
文摘Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associated gene.The abnormal expansion translates into a protein bearing an abnormally long tract of glutamines.
文摘The main function of neurons is information transmission in the form of action potentials.To fulfill this duty,neurons are connected functionally with each other via synapses,the microscopic structures where specialized molecular machinery is strategically placed to release and receive neurotransmitters and to generate and extinguish calcium(Ca^(2+))signals.These synaptic molecular components are highly dynamic and they influence each other to confer structural and functional adaptability(plasticity)to neuronal communication(Biederer et al.,2017).
基金supported by the National Natural Science Foundation of China,No.81271286 to YUAN Fang and No.81228009 to YANG Shao Hua
文摘Objective To investigate the role of extracellular signal-regulated kinase1/2(ERK1/2) pathway in the regulation of aquaporin 4(AQP4) expression in cultured astrocytes after scratch-injury. Methods The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase(LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2(p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 μmol/L U0126(ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups. Results Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury. Conclusion These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.
基金supported in part by the Institute for Basic Science(to HP)No.IBS-R015-D1
文摘Attention deficit hyperactivity disorder(ADHD) is a pervasive psychiatric disorder that affects both children and adults. Adult male and female patients with ADHD are differentially affected, but few studies have explored the differences. The purpose of this study was to quantify differences between adult male and female patients with ADHD based on neuroimaging and connectivity analysis. Resting-state functional magnetic resonance imaging scans were obtained and preprocessed in 82 patients. Group-wise differences between male and female patients were quantified using degree centrality for different brain regions. The medial-, middle-, and inferior-frontal gyrus, superior parietal lobule, precuneus, supramarginal gyrus, superior- and middle-temporal gyrus, middle occipital gyrus, and cuneus were identified as regions with significant group-wise differences. The identified regions were correlated with clinical scores reflecting depression and anxiety and significant correlations were found. Adult ADHD patients exhibit different levels of depression and anxiety depending on sex, and our study provides insight into how changes in brain circuitry might differentially impact male and female ADHD patients.
基金Supported by The Natural Science Fund of Fujian Province,No.C0910595 and No.2012J05053Science Fund and Doctor Initial Fund of FMU,No.09ZD009 and No.2010BS008
文摘AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously.Visceral hypersensitivity was evaluated using electromyographic(EMG)responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions(CRD).Abdominal withdrawal reflex(AWR)scores and pain thresholds were also detected in adult rats.Different doses of ZD7288(25,50,and 100 nmol/L)were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.RESULTS:EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats(P<0.05).The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats(P<0.05).Treatment with50-100 nmol/L ZD 7288 significantly inhibited EMG responses(16%-62%,80-20 mmHg CRD,P<0.05)and AWR scores(24%-37%,40-20 mmHg CRD,P<0.05;12%-61%,80-20 mmHg CRD,P<0.05,respectively),and significantly increased pain thresholds(32%-77%,P<0.05).CONCLUSION:Spinal HCN channels may play an important role in chronic visceral hypersensitivity.
基金supported by Ministry of Higher education,Government of Malaysia,under the grant No.RAGS/2013/UITM/SKK03/2[UiTM file no.600-RMI/RAGS 5/3(103/2013)]the Institut Pengurusan Penyelidikan(RMI),Universiti Teknologi MARA,Malaysia,under the grant 600-IRMI/MyRA 5/3/LESTARI(0088/2016).
文摘Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against NMDA-induced retinal damage.In this study,Sprague-Dawley rats were randomized to undergo intravitreal injection of vehicle,NMDA or MgAT as pre-treatment to NMDA.Seven days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRN3A immunostaining.Functional outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain reaction.Retinal phospho-NF-κB,phospho-p53 and AP-1 levels were evaluated using western blot assay.Rat visual functions were evaluated using visual object recognition tests.Both retrograde labelling and BRN3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of NMDA.Electroretinography indicated that pre-treatment with MgAT partially preserved the functional activity of NMDA-exposed retinas.MgAT abolished NMDA-induced increase of retinal phospho-NF-κB,phospho-p53 and AP-1 expression and suppressed NMDA-induced transcriptional activity of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(i.e.objects with different shapes)after NMDA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with MgAT.In conclusion,pre-treatment with MgAT prevents NMDA induced retinal injury by inhibiting NMDA-induced neuronal apoptosis via downregulation of transcriptional activity of NF-κB,p53 and AP-1-mediated c-Jun/c-Fos.The experiments were approved by the Animal Ethics Committee of Universiti Teknologi MARA(UiTM),Malaysia,UiTM CARE No 118/2015 on December 4,2015 and UiTM CARE No 220/7/2017 on December 8,2017 and Ethics Committee of Belgorod State National Research University,Russia,No 02/20 on January 10,2020.
